Neophilia is a primary behavioral trait that strongly correlates with resilience to a wide range of stressors. Confinement stress reduces neophilic exploration in many species, and represents a major life stressor for refugees, kidnapped victims, and the incarcerated. High levels of neophilia are correlated with a resilience to confinement stress. There is an immediate need to better understand how novelty seeking behavior is encoded and modulated within a central nervous system to better understand how to manage the health of at risk populations. The neuronal and molecular dissection of novelty-seeking in a genetic model system would greatly facilitate reaching this objective. This project's long-term goal is to develop a deeper understanding of the neurobiology of neophilic behavior. This goal will be use Drosophila melanogaster as a model organism for dissecting novelty-driven exploration. The overall objective of this proposal is to use genetic and transgenic approaches in Drosophila to define the serotonergic circuits responsible for changing the rate of novelty habituation during exploration of an open field arena, and to determine the role of these circuits in the confinement induced reductions in exploratory behavior found in Drosophila. The central hypothesis is that serotonin alters exploration by modulating neural circuits involved in responding to novel stimuli, and that these circuits are also responsible for the impact of confinement on neophilic behavior. Both increased serotonin signaling and confinement act to decrease the behavioral responsiveness to novel stimuli during the habituation of these stimuli. In the proposed work, defined serotonergic microcircuits will be isolated and examined for effects on the rate of novelty habituation. The rationale behind this proposal is that the dissection of exploration in a model system will provide critical insights into the potential mechanisms that serotonin has in modulating the conserved responsiveness to novel stimuli. This proposal is significant as it will reduce the complexity of the serotonergic systems to single microcircuits and receptor classes, and allow for the determination of the precise roles of these pre- and post-synaptic neurons in novelty-driven exploration. This proposal is innovative as it will take advantage of an experimentally powerful and accessible neural and behavioral genetic model system to dissect the serotonin receptors and the circuits required for neophilic behavior. Novelty-Seeking behavior has not yet been dissected systematically with neural genetic approaches in any system. The completion of this proposal will provide a much more detailed understanding of how serotonin modulates novelty-driven exploration, the neurons involved, and the receptors that are necessary for this modulation in a relatively simple system. Moreover, we will specifically determine how serotonin regulates the effect of confinement on neophilic exploration in this system. These data will provide a logical framework for encoding novelty seeking and how this impacts other behavioral traits.